In a previous chapter, I illustrated how pesticides can affect brain development and lead to autism. Here, before continuing the discussion of the long list of factors that can lead to the same outcomes, I’ll revisit the key principles of brain maturation to better understand how these factors come into play and result in developmental disorders.
Building a brain with its million billion synaptic connections is no easy task. The general idea is that this development is not simply a sequence of genes directing each step, but rather a continuous interaction between genes and the environment. Indeed, the developing brain exhibits unique activities that are specific to it, and throughout the process, these activities modulate brain development. Thus, in all animal species, including humans, in the immature brain, the retina responds to a light stimulus with a “retinal wave”—a prolonged response that does not enable vision and serves no sensory purpose. However, if this activity is blocked in utero, the visual system develops abnormally, suggesting that this activity—which has no sensory purpose—is crucial for brain development. Similarly, in a premature infant or a moving baby, the command often does not come from the cortex—as it does in adults—but from the periphery, suggesting that this activity serves to inform the brain about its connections. Furthermore, virtually all essential functions of brain development are modulated by signals from the internal and external environment (see image). This is true of cell division and proliferation, migration, synapse formation, and the formation of neural networks. Genes and the environment interact at all these stages.
In 2010, together with my colleague and friend Prof. Nick Spitzer from California, I proposed the concept of “checkpoints.” The idea is that checkpoints verify at each stage that the connections are correct—a sort of quality control. Much like the construction of a building, there is a general plan, but then comes the actual construction process itself, with its site meetings and verification that everything is proceeding as planned. The general plan outlines the broad strokes of construction; even in the absence of neural activity, the brain’s major structures will be in place but will not be functional. This concept, which has been validated in numerous animal species—ranging from lampreys to rodents—is fundamental to understanding the process and has abundant clinical implications. It helps explain why so many functions and types of in utero events can impact brain development and result in autism or other neurodevelopmental syndromes.
In the following chapters, I will describe the list of events that impact maturation and are specifically linked to autism.
